1,25-二羟维生素D_3对糖尿病肾病大鼠足细胞Angptl4、Desmin表达的影响  

Effects of 1,25-dihydroxy-vitamin D_3 on expression of Angptl4 and Desmin of podocytes in rats with diabetic nephropathy

作　　者：吴欣[1] 黄健[1] 刘畅[1] 杨静[1] 阳柳[1] 黄匀 李晓颖[1] 于黔[1] WU Xin;HUANG Jian;LIU Chang;YANG Jing;YANG Liu;HUANG Yun;LI Xiaoying;YU Qian(The First People＇ s Hospital of Guiyang,Guizhou 550002,Chin)

机构地区：[1]贵阳市第一人民医院,贵阳550002

出　　处：《山东医药》2018年第30期40-43,共4页Shandong Medical Journal

基　　金：贵州省贵阳市科技局科技计划项目[(筑科合同2016001)09号]

摘　　要：目的探讨1,25-二羟维维生素D3[1,25-(OH)_2D_3]对糖尿病肾病(DN)大鼠足细胞损伤的影响及其可能的机制。方法选择雄性SD大鼠30只,取其中22只采用一次性腹腔注射STZ的方法制备糖尿病模型,将造模成功的18只大鼠随机分为DN模型组(M组)、1,25-(OH)_2D_3干预组(D组)各9只,另将未造模的8只大鼠作为正常对照组(N组)。D组在DN模型建立后予1,25-(OH)_2D_30.1μg/(kg·d)灌胃,M组给予等量橄榄油灌胃,N组给予等量蒸馏水灌胃。均干预12周后,收集各组大鼠24 h尿液,采用双缩尿法测定24 h尿蛋白(24 h Upro),采用ELISA法测定尿血管生成素样蛋白4(Angptl4)水平。眼球取血,分离血清,采用全自动生化分析仪测定血BUN、SCr水平,采用ELISA法测定血Angptl4水平。取各组大鼠右肾组织,采用HE染色观察肾组织病理变化。取各组大鼠肾组织,分别采用免疫组化SP法、Western blotting法检测肾组织Angptl4、结蛋白(Desmin)蛋白表达。结果与N组相比,M组、D组24 h Upro、尿Angptl4、血BUN、Scr均升高,血Angptl4水平均降低(P均<0.05);与M组相比,D组24 h Upr、尿Angptl4、血BUN、Scr均降低,血Angptl4水平升高(P均<0.05)。病理检查示,M组可见毛细血管球肥大,肾小球基底膜部分增厚,系膜增生。电镜结果示,M组肾小球基底膜增厚、足突融合,D组肾脏病理改变较M组减轻。与N组相比,M组肾组织Angptl4、Desmin蛋白表达均上调(P均<0.05);与M组相比,D组肾组织Angptl4、Desmin蛋白表达均下调(P均<0.05)。结论 1,25-(OH)_2D_3可减轻DN大鼠的肾损伤,其机制可能与抑制足细胞分泌Angptl4、Desmin蛋白,从而发挥对肾小球足细胞的保护作用有关。Objective To investigate the effects of 1,25-dihydroxy vitamin D3[1,25-（OH）2D3]on podocyte injury in rats with diabetic nephropathy（ DN） and its possible mechanism. Methods Thirty male SD rats were selected and 22 of them were chosen to prepare the DN models by one-time intraperitoneal injection of STZ. The 18 rats were randomly divided into the DN model group（ group M） and 1,25-（OH）2D3 intervention group（ group D）,with 9 in each; in addition,8 rats without treatment were taken as the normal control group（ group N）. Rats in the group D were injected with 1,25-（OH）2D30. 1 μg/（ kg·d） after the establishment of DN models. The rats in the group M were given equal amount of olive oil for gavage,while the N group was given the same amount of distilled water for gavage. After 12 weeks of intervention,24 h urine was collected from each group,24 h urine protein（ 24 h Upro） was measured by double reduction method,and Angptl4 level was measured by ELISA. Blood was collected from eyeballs and the serum was separated. Blood BUN and SCr levels were measured by automatic biochemical analyzer. Blood Angptl4 level was measured by ELISA. The right kidney tissues of each group were taken and the pathological changes were observed by HE staining. The kidney tissues of each group were collected,and the expression of Angptl4 and Desmin protein was detected by immunohistochemistry and Western blotting,respectively. Results Compared with group N,24 h Upr,urine Angptl4,blood BUN,and Scr increased in the group M and group D,and blood Angptl4 level decreased（ all P〈0. 05）. Compared with group M,24 h Upr,urine Angptl4,blood BUN,and Scr decreased in the group D,and blood Angptl4 level increased（ all P〈0. 05）. Pathological findings： in the group M,the glomerular hypertrophy was observed,the glomerular basement membrane partly thickened,and mesangial hyperplasia was obvious. The results of electron microscopy showed that the glomerular basement membrane was thickened and the foot process was

关 键 词：糖尿病肾病 足细胞 1 25-二羟维生素D3 血管生成素样蛋白4 结蛋白 

分 类 号：R587.2[医药卫生—内分泌]